Histone deacetylase 10-promoted autophagy as a druggable point of interference to improve the treatment response of advanced neuroblastomas

Abstract

Neuroblastoma is the most common extracranial solid tumor in childhood. Despite intense multimodal therapy and many improvements through basic scientific and clinical research, the successful response of advanced-stage patients to chemotherapy remains poor. Autophagy is a cytoprotective mechanism that may help advanced cancer cells survive stressful conditions such as chemotherapy. Here we review our recent findings describing HDAC10 as a promoter of autophagy-mediated survival in neuroblastoma cells and identifying this HDAC isozyme as a druggable regulator of advanced-stage tumor cell survival. These results propose a new and promising way to considerably improve treatment response in the neuroblastoma patient subgroup with the poorest outcome.

A Next Generation Connectivity Map: L1000 Platform And The First 1,000,000 Profiles

“…Hierarchical clustering of pairwise connectivities of the HDAC inhibitor PCL members reveals substructure within the class. The pan-HDAC inhibitors generally cluster together, distinct from the more isoform-selective compounds, suggesting that gene expression can be used to further stratify compounds within the same class (Fass et al 2010;Bradner et al 2010;Butler et al 2010;Kwon et al 1998;Arts et al 2009;Haggarty et al 2003;Bantscheff et al 2011;Oehme et al 2013;Balasubramanian et al 2008)…”

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

“…However, since it lacks a ubiquitin-binding domain and tubulin deacetylase activity there may be no functional overlap with HDAC6. 10 Only recently, it has been reported to influence neuroblastoma cell survival by promoting autophagy, 45 but to suppress cervical cancer metastasis. 46 In contrast, increased HDAC10 expression in chronic lymphocytic leukemia patients was associated with poor prognosis.…”

Epigenetic modifications as regulatory elements of autophagy in cancer

“…Further studies support that promoter methylation of ASS1 sensitized lymphomas or glioblastomas to arginine deiminase treatment [96]. Histone deacetylase 10 promoted autophagy as a druggable point of interference to improve the treatment response of advanced neuroblastomas [97]. Currently, HDAC inhibitors are attracting more and more attention in anticancer treatments.…”